4.6 Article

Blinatumomab for HLA loss relapse after haploidentical hematopoietic stem cell transplantation

Journal

AMERICAN JOURNAL OF CANCER RESEARCH
Volume 11, Issue 6, Pages 3111-3122

Publisher

E-CENTURY PUBLISHING CORP

Keywords

B-cell acute lymphoblastic leukemia; HLA loss relapse; blinatumomab

Categories

Funding

  1. National Natural Science Foundation of China [81730008]
  2. Key Research and Development Program of Zhejiang Province [2019C03016]

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The loss of patient-specific HLA after haploidentical hematopoietic stem cell transplantation is considered a relapse mechanism affecting graft-versus-leukemia (GVL) effects. Blinatumomab showed promising results in treating patients with HLA loss relapse, with most patients achieving complete remission or partial recovery within the first treatment cycle and meeting the primary endpoint within 2 cycles. Adverse effects included cytokine release syndrome, cytopenias, and elevated liver enzymes. Further studies are needed to assess the efficacy of blinatumomab in this patient population.
Loss of patient-specific HLA after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is considered as a relapse mechanism for lacking the incompatible molecule to elicit alloreactivity, which extensively diminishing graft-versus-leukemia (GVL) effects. Blinatumomab, as a CD3/CD19 bispecific antibody, can yield a profound response via redirecting T cells towards malignant lymphoblasts in B-cell acute lymphoblastic leukemia (B-ALL). We aimed to assess the feasibility of blinatumomab in treating patients with HLA loss relapse after haplo-HSCT. Four eligible patients undergoing HLA loss relapse after haplo-HSCT were enrolled in the study. Four patients achieved a complete remission/complete remission with partial he-matologic recovery (CR/CRh) with three minimal residual disease (MRD)-negative response within the first cycle of treatment. Three of the four met a primary endpoint with CR/CRh and MRD-negative response within 2 cycles of treatment. One patient developed new extramedullary sites of skin after the first cycle. Cytokine release syndrome was observed in one patient. Cytopenias, as well as elevated alanine aminotransferase and aspartate aminotransferase, were two common adverse effects during treatment. By redirecting lysis of CD19-positive lymphoblast who losing the incompatible HLA, blinatumomab is a potential strategy to eradicate malignant cells via restoring GVL effects. A randomized clinical trial assessing blinatumomab in patients with HLA loss relapse after HSCT is warranted.

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